Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a major global impact. Due to the limitations of current treatments and adverse effects, there is increasing interest in natural compounds with therapeutic potential. Mansorina (MA), a coumarin from Mansonia gagei, has antioxidant and anti-inflammatory properties. The present study aims to evaluate the effects of MA on memory, using zebrafish as a preclinical model for AD.

To induce an Alzheimer's disease-like amnesia model, zebrafish (Danio rerio) were exposed to okadaic acid (OKA, 10 nM) for 4 days. Six groups (n = 10/group) were formed: control (DMSO), GAL (1 mg/L), OKA, and OKA co-treated with mansorine (MA) at 1, 3, or 6 μg/L. MA was administered for 7 days, every 3 days, during water changes. Cognitive functions were assessed by Y-maze tests (spatial memory and locomotor activity) and novel object recognition (NOR). Behavioral data were analyzed with one-way ANOVA and Tukey's test (GraphPad Prism 9, p < 0.05).

OKA treatment significantly impaired spatial memory and object recognition in zebrafish, as evidenced by decreased time spent in the novel arm (Y-maze) and novel object preference (NOR) (p < 0.0001). GAL improved both parameters, confirming its cognitive effects. Co-treatment with MA (3 and 6 μg/L) significantly reversed these deficits (p < 0.001 – p < 0.00001), increasing exploration of the novel arm and object. MA also increased locomotor activity, suggesting a stimulant effect. The results support the neuroprotective role of MA.

The results of this study show that the administration of mansorine (MA) to okadaic acid (OKA)-treated fish increased exploratory behavior, as evidenced by novel arm preference in the Y-maze test, and improved recognition memory in the NOR test. MA also contributed to the restoration of cholinergic deficit and the improvement of dementia symptoms, supporting its neuroprotective potential.